Kay R A, Ollier W E
ACR Epidemiology Research Unit, Manchester, Grande Bretagne, UK.
Rev Rhum Ed Fr. 1994;61(7-8):532-45.
Animal models have demonstrated that the T-cell repertoire is restricted when the response to defined autoantigens is studied. Anti-V beta specific monoclonal antibodies or specific V beta-derived peptides can be used to manipulate autoreactive T-cells to either prevent or treat established experimental disease in animals. In some animal models of arthritis, inherited differences in the TCR repertoire can protect against the development of experimental autoimmune disease. Human studies have generally given conflicting results with regard to the role of the TCR complexes as susceptibility loci for disease. This may be due to the heterogeneity present in the human population and/or in the diseases studied. In some diseases, where there is convincing evidence for putative autoantigens (multiple sclerosis) or distinct immunodysfunctional pathology (hypergammaglobulinaemic primary Sjögren's syndrome), restricted TCR repertoires and germline TCR susceptibility loci can be discerned. Recent evidence suggests that autoimmune disease may eventually be mapped to regulatory regions of the TCR V genes rather than the allelic differences in coding region structure. This may have implications for the future therapy of autoimmune rheumatic disease.
动物模型已表明，在研究对特定自身抗原的反应时，T细胞库是受限的。抗Vβ特异性单克隆抗体或特定的Vβ衍生肽可用于操控自身反应性T细胞，以预防或治疗动物已患的实验性疾病。在一些关节炎动物模型中，TCR库中的遗传差异可预防实验性自身免疫疾病的发生。关于TCR复合物作为疾病易感基因座的作用，人体研究通常给出了相互矛盾的结果。这可能是由于人群中以及所研究疾病中存在的异质性。在一些疾病中，有令人信服的证据证明存在假定的自身抗原（如多发性硬化症）或明显的免疫功能失调病理学特征（如高球蛋白血症性原发性干燥综合征），此时可辨别出受限的TCR库和种系TCR易感基因座。最近的证据表明，自身免疫疾病最终可能定位到TCR V基因的调控区域，而非编码区结构中的等位基因差异。这可能对自身免疫性风湿病的未来治疗具有重要意义。
